Mycobacterium tuberculosis (MTB) multiplies and persists within macrophages. One component of this environment is the presence of host lipids. MTB secretes all classes of phospholipases and within granulomatous lesions it likely degrades host lipids leading to three possible effects: (1) free fatty acids are liberated and provide carbon and energy; (2) some free fatty acids have growth inhibiting properties and may induce bacterial latency; or (3) hydrolysis of host phospholipids may release arachidonic acid (AA) and diacylglycerol (DAG) and these may serve as signaling molecules that modulate inflammation or immunity. These hypotheses will be tested in three steps. First, whole genome expression profiling will be conducted of MTB growing in media containing fatty acids, phospholipids or lipid bilayers as the sole carbon source. Second, genes coding for functions predicted to be essential for lipid degradation or assimilation will be inactivated. Third, these mutants will be tested with respect to their ability to utilize lipid substrates, survive in macrophages or activate (AA) or (AA) mediated pathways.